Haplotype analysis of XRCC1 gene polymorphisms and the risk of thyroid carcinoma

Variants in DNA repair genes may alter the repair mechanisms that make the persons vulnerable to DNA damage. These polymorphic variants in the DNA repair pathway genes, such as XRCC1, have been associated with susceptibility of several types of cancer including thyroid cancer. This study was designed to explore the link between XRCC1 polymorphisms and modulation of thyroid cancer risk.

Our study consisted of 456 thyroid cancer patients and 400 controls. For XRCC1 polymorphisms analyses, three single nucleotide polymorphisms (SNPs) (rs25489, rs25487 and 1799782) were selected and genotyped by ARMS-PCR.

The homozygous mutant (AA) of rs25489 SNP showed highly significant association with thyroid cancer risk (OR=0.17; 95% CI=0.10-0.31; p=0.0001). In the rs25487 polymorphism all genotypes showed no significantly increased risk of thyroid cancer in patients compared to controls (p>0.05). In the rs1799782 of XRCC1 gene, the homozygous mutant (TT) significantly decreased the risk of thyroid cancer (OR=0.71; 95% CI=0.50-1.01; p=0.05). Eight haplotypes were generated for three selected SNPs (rs25489, rs25487 and rs1799782) of XRCC1 gene among thyroid cases and controls. The haplotype GAT (OR=1.69; 95% CI=1.25- 2.30; p=0.0005) and GGC (OR=2.75; 95% CI=2.11-3.58; p=1.29e-014) showed highly significant association with increased risk of thyroid cancer. The haplotypes AAC (OR=0.31; 95% CI=0.17-0.57; p=6.68e-005), AAT (OR= 0.51; 95% CI=0.34-0.78; p=0.001), AGT (OR=0.46; 95%CI=0.29- 0.71; p=0.0003) and GGT (OR=0.80; 95% CI=0.64-0.98; p=0.03) had significant reducing effect in thyroid cancer patients.

XRCC1 Arg280His and Arg194Trp were associated with thyroid cancer in Pakistani population. These genetic markers may provide an insight into the disease pathogenesis and help open novel therapeutic strategies for thyroid cancer.